Novel acyl sulfonamide LY573636-sodium: effect on hematopoietic malignant cells.
LY573636-sodium is a promising anti-tumor agent, which causes growth arrest and apoptosis of a variety of human solid tumors in vitro and in vivo. Moreover, studies have shown that the compound is selectively toxic towards tumor cells over their normal counterparts. This targeted effect makes LY573636 a candidate for combined therapy regimens in patients with advanced or resistant cancers. We studied for the first time, the anti-tumor properties of LY573636 against a variety of human hematopoietic malignancies, including AML, B-ALL, large B-cell and mantle cell lymphoma cell lines. Cells were treated with the compound in vitro and its effect on cell proliferation, apoptosis and differentiation was determined. The cell lines underwent growth arrest in response to treatment with LY573636 in a dose-dependent manner. This antiproliferative activity was associated with the induction of apoptosis, loss of mitochondrial membrane potential and induction of reactive oxygen species. Furthermore, we showed that LY573636 was able to induce granulocytic/monocytic differentiation of HL60 and U937 cells. LY573636, as shown before in solid tumors, is effective in hematopoietic cell lines as well. These data suggest the use of LY573636 alone or in combination with conventional chemotherapeutic regimens in hematopoietic malignancies.
Haritunians
Talin
T
Division of Hematology/Oncology, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, CA 90048, USA.
Gueller
Saskia
S
O'Kelly
James
J
Ilaria
Robert
R
Koeffler
H Phillip
HP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; C534068:N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide; D017382:Reactive Oxygen Species; D013449:Sulfonamides